Immune System

I INTRODUCTION

Human Anatomy Illustrations

Learn about the ten systems in the human body.
© Microsoft Corporation. All Rights Reserved.

Immune System, group of cells, molecules, and organs that act together to
defend the body against foreign invaders that may cause disease, such as
bacteria, viruses, and fungi. The health of the body is dependent on the
immune system’s ability to recognize and then repel or destroy these
invaders.

II IMMUNITY: INNATE AND ADAPTIVE

Most animals have systems that resist disease. The disease resistance
provided by these systems is called immunity. There are two types of
immunity: innate and adaptive. Innate, or nonspecific, immunity is the
body’s first, generalized line of defense against all invaders. Innate immunity
is furnished by barriers such as skin, tears, mucus, and saliva, as well as by
the rapid inflammation of tissues that takes place shortly after injury or
infection. These innate immune mechanisms hinder the entrance and spread
of disease but can rarely prevent disease completely.

If an invader gets past this first line of defense, the cells, molecules, and
organs of the immune system develop specifically tailored defenses against
the invader. The immune system can call upon these defenses whenever this
particular invader attacks again in the future. These specifically adapted
defenses are known as adaptive, or specific, immunity.

Adaptive immunity has four distinguishing properties: First, it responds only

after the invader is present. Second, it is specific, tailoring each response to
act only on a specific type of invader. Third, it displays memory, responding
better after the first exposure to an invader, even if the second exposure is
years later. Fourth, it does not usually attack normal body components, only
those substances it recognizes as nonself.

Adaptive immune responses are actually reactions of the immune system to

structures on the surface of the invading organism called antigens. There are
two types of adaptive immune responses: humoral and cell mediated. During
humoral immune responses, proteins called antibodies, which can stick to
and destroy antigens, appear in the blood and other body fluids. Humoral
immune responses resist invaders that act outside of cells, such as bacteria
and toxins (poisonous substances produced by living organisms). Humoral
immune responses can also prevent viruses from entering cells.

During cell-mediated immune responses, cells that can destroy other cells
become active. Their destructive activity is limited to cells that are either
infected with, or producing, a specific antigen. Cell-mediated immune
responses resist invaders that reproduce within the body cells, such as
viruses. Cell-mediated responses may also destroy cells making mutated
(changed) forms of normal molecules, as in some cancers.

III COMPONENTS OF THE IMMUNE SYSTEM

The ability of the immune system to mount a response to disease is

dependent on many complex interactions between the components of the
immune system and the antigens on the invading pathogens, or disease-
causing agents.

Macrophage
A s
Macrophage Engulfing Bacterium
A macrophage, in yellow, engulfs and consumes a bacterium. Macrophages
are large phagocytes, cells that wander through the body consuming foreign
particles such as dust, asbestos particles, and bacteria. They help protect the
body against infection.
Dennis Kunkel/CNRI/Phototake NYC

White blood cells are the mainstay of the immune system. Some white blood
cells, known as macrophages, play a function in innate immunity by
surrounding, ingesting, and destroying invading bacteria and other foreign
organisms in a process called phagocytosis (literally, “cell eating”), which is
part of the inflammatory reaction. Macrophages also play an important role
in adaptive immunity in that they attach to invading antigens and deliver
them to be destroyed by other components of the adaptive immune system.

Lymphocyte
B s
Lymphocyte
Scanning electron micrograph of a normal T lymphocyte. T lymphocytes are
specialized white blood cells that identify and destroy invading organisms
such as bacteria and viruses. Some T lymphocytes directly destroy invading
organisms, whereas other T lymphocytes regulate the immune system by
directing immune responses.
NIBSC/Science Source/Photo Researchers, Inc.

Lymphocytes are specialized white blood cells whose function is to identify

and destroy invading antigens. All lymphocytes begin as “stem cells” in the
bone marrow, the soft tissue that fills most bone cavities, but they mature in
two different places. Some lymphocytes mature in the bone marrow and are
called B lymphocytes. B lymphocytes, or B cells, make antibodies, which
circulate through the blood and other body fluids, binding to antigens and
helping to destroy them in humoral immune responses.

Other lymphocytes, called T lymphocytes, or T cells, mature in the thymus, a

small glandular organ located behind the breastbone. Some T lymphocytes,
called cytotoxic (cell-poisoning) or killer T lymphocytes, generate cell-
mediated immune responses, directly destroying cells that have specific
antigens on their surface that are recognized by the killer T cells. Helper T
lymphocytes, a second kind of T lymphocyte, regulate the immune system
by controlling the strength and quality of all immune responses.

Most contact between antigens and lymphocytes occurs in the lymphoid

organs—the lymph nodes, spleen, and tonsils, as well as specialized areas of
the intestine and lungs (see Lymphatic System). Mature lymphocytes
constantly travel through the blood to the lymphoid organs and then back to
the blood again. This recirculation ensures that the body is continuously
monitored for invading substances.

Antigen
C Receptors

One of the characteristics of adaptive immunity is that it is specific: Each

response is tailored to a specific type of invading antigen. Each lymphocyte,
as it matures, makes an antigen receptor—that is, a specific structure on its
surface that can bind with a matching structure on the antigen like a lock
and key. Although lymphocytes can make billions of different kinds of
antigen receptors, each individual lymphocyte makes only one kind. When
an antigen enters the body, it activates only the lymphocytes whose
receptors match up with it.

Antigen-Presenting
D Cells

When an antigen enters a body cell, certain transport molecules within the
cell attach themselves to the antigen and transport it to the surface of the
cell, where they “present” the antigen to T lymphocytes. These transport
molecules are made by a group of genes called the major histocompatibility
complex (MHC) and are therefore known as MHC molecules. Some MHC
molecules, called class I MHC molecules, present antigens to killer T cells;
other MHC molecules, called class II MHC molecules, present antigens to
helper T cells.

IV HUMORAL IMMUNE RESPONSE

The humoral immune response involves a complex series of events after

antigens enter the body. First, macrophages take up some of the antigen
and attach it to class II MHC molecules, which then present the antigen to T
helper cells. The T helper cells bind the presented antigen, which stimulates
the T helper cells to divide and secrete stimulatory molecules called
interleukins. The interleukins in turn activate any B lymphocytes that have
also bound the antigen. The activated B cells then divide and secrete
antibodies. Finally, the secreted antibodies bind the antigen and help destroy
it.

A Antibodies
Antibodies are Y-shaped proteins called immunoglobulins (Ig) and are made
only by B cells. The antibody binds to the antigen at the ends of the arms of
the Y. The area at the base of the Y determines how the antibody will destroy
the antigen. This area is used to categorize antibodies into five main classes:
IgM, IgG, IgA, IgD, and IgE. During the humoral immune response, IgM is the
first class of antibody made. After several days, other classes appear. Exactly
which other Ig classes a B cell makes depends on the kind of interleukins it
receives from the T helper cells.

Antibodies can sometimes stop an antigen’s disease-causing activities simply

by neutralization—that is, by binding the antigen and preventing it from
interfering with the cell’s normal activities. For example, the toxin made by
tetanus bacteria binds to nerve cells and interferes with their control of
muscles. Antibodies against tetanus toxin stick to the toxin and cover the
part of it that binds to nerve cells, thereby preventing serious disease. All
classes of antibodies can neutralize antigens.

Antibodies also help destroy antigens by preparing them for ingestion by

macrophages in a process called opsonization. In opsonization, antibodies
coat the surface of antigens. Since macrophages have receptors that stick to
the base of the antibody’s Y structure, antigens coated with antibodies are
more likely to stick to the macrophages and be ingested. Opsonization is
especially important in helping the body resist bacterial diseases.

Finally, IgM and IgG antibodies can trigger the complement system, a group
of proteins that cause cells to disintegrate by cutting holes in the cell
membrane. Complement is important in resisting bacteria that are hard to
destroy in other ways. For example, some of the bacteria that cause
pneumonia have a slimy coating, making it hard for macrophages to ingest
and eliminate them. However, if IgM and IgG antibodies bind to the
pneumonia bacteria and activate the complement system, it is able to cut
holes in the bacteria to destroy them.

Although the IgM and IgG classes of antibodies work best in the circulatory
system, IgA can exit the bloodstream and appear in other body fluids. IgA is
thus important in preventing infection at mucosal surfaces, such as the
intestine and the lung. Since these are the sites where most infectious
agents enter, IgA is particularly important in resistance to many diseases.
IgA is also found in mother’s milk and may help nursing newborns resist
disease.

V CELL-MEDIATED IMMUNE RESPONSE

As with the humoral immune response, the cell-mediated immune response
involves a complex series of events after antigens enter the body. Helper T
cells are required, so some of the antigen must be taken up by macrophages
and presented to helper T cells. The helper T cells bind the presented
antigen and thereby become activated to divide and secrete interleukins.
The interleukins in turn activate any killer T cells that have already bound
antigen attached to class I MHC molecules on infected cells. The activated
killer T cells can then kill any cells displaying antigen attached to class I MHC
molecules, effectively eliminating any cells infected with the antigen.

VI IMMUNIZATION

Immunization Schedule for Infants and Children

Physicians recommend that infants and children receive vaccinations to
protect them from highly contagious diseases. Many vaccines require more
than one dose to provide full immunity, and sometimes combination
vaccines are used to lessen the number of injections a child receives. This
chart provides the ages for immunization with specific vaccines that the
American Academy of Pediatrics recommends for children living in the United
States.
© Microsoft Corporation. All Rights Reserved.

When the body is first exposed to an antigen, several days pass before the
adaptive immune response becomes active. Immune activity then rises,
levels off, and falls. During following exposures to the same antigen, the
immune system responds much more quickly and reaches higher levels.
Because the first, or primary, immune response is slow, it cannot prevent
disease, although it may help in recovery. In contrast, subsequent, or
secondary, immune responses usually can prevent disease because the
pathogen is detected, attacked, and destroyed before symptoms appear.
This complete resistance to disease is called immunity and may be achieved
through either active or passive immunization.

Active
A Immunization

Active immunization occurs when a person’s own immune system is

activated and generates a primary immune response. Active immunization
can be triggered in two ways, either by natural immunization or by
vaccination.

In natural immunization, the body contracts a disease and recovers. Because

a primary immune response occurs during the illness, the immune system
will mount a disease-preventing secondary response every time it is
subsequently exposed to the disease. Natural immunization is developed
during childhood diseases, such as chicken pox. After having had the disease
once, a person is no longer susceptible to it.

Vaccination is intentional immunization against a particular disease by the

use of vaccines, substances that are structurally similar to the actual
disease-producing agents but that do not produce disease themselves. Most
vaccines take one of two forms. The first type of vaccine, such as the
vaccines for tetanus and whooping cough, contains chemically killed bacteria
or other pathogenic organisms. The other type, such as the oral polio
vaccine, contains weakened forms of living organisms that have been
genetically selected so they do not produce disease.

B Passive Immunization

Another way to provide immunity is by means of passive immunization.

Passive immunization does not engage the person’s own immune system.
Instead, the individual receives antibodies that were created in another
person or animal. Such antibodies can be lifesaving when a disease
progresses too rapidly for natural immunization to occur. For example, if a
person who has not been immunized against tetanus bacteria is exposed to
tetanus, the toxin produced by these bacteria would reach a deadly level
before a primary immune response could begin. Administering antibodies
against tetanus toxin quickly neutralizes the toxin and prevents death.

Passive immunization has two drawbacks: First, the person does not mount
an active immune response, so the immunizing effect is temporary and the
person is not immune after recovery. Second, if passive immunization is
used repeatedly, it occasionally produces side effects.
VII IMMUNE SYSTEM DISORDERS

Disorders of the immune system can range from the less serious, such as
mild allergy, to the life threatening, such as more serious allergy, transplant
rejection, immune deficiencies, and autoimmune diseases.

A Allergy

Allergy, sometimes called hypersensitivity, is caused by immune responses

to some antigens. Antigens that provoke an allergic response are known as
allergens. The two major categories of allergic reaction, rapid and delayed,
correspond to the two major types of immune responses.

Rapid allergic reactions, such as those to bee venom, pollen or pets, are
caused by humoral immune mechanisms. These immediate hypersensitivity
reactions result from the production of IgE antibodies when a person is first
exposed to an allergen. The IgE antibodies become attached to mast cells—
white blood cells containing histamine, the chemical that causes the familiar
allergic symptoms of runny nose, watery eyes, and sneezing. Mast cells are
particularly abundant in the lungs and intestine. If the antigen-binding sites
of mast cells become filled with an allergen, the mast cells release
histamine.

Allergic reactions that are slow in onset (known as delayed-type

hypersensitivity, or DTH), such as those to poison ivy or poison oak, are cell
mediated. Extreme examples of DTH occur when macrophages cannot easily
destroy invading substances. As a result, T cells are activated, leading to
inflammation of the body tissue. This inflammation continues for as long as
the T cells are activated. The bacterium that causes tuberculosis also falls
into this category because this bacterium is covered with a waxy coat that
macrophages cannot destroy. The resulting DTH leads to the lung and liver
damage associated with tuberculosis.

B Transplant Rejection

The immune system recognizes and attacks anything different from the
substances normally present within an individual, even substances that are
only slightly different, such as transplanted tissues and organs (see
Transplantation, Medical).

When an organ is transplanted, the MHC of the donor organ is recognized as

foreign and attacked by the recipient’s immune system. To minimize the
chances of transplant rejection, physicians seek transplant donors who share
as many MHC genes as possible with the transplant recipient. Even then,
most transplant recipients are given drugs to suppress their immune
response and prevent rejection of the transplant.

If the transplanted tissue contains T lymphocytes from the donor, as in bone

marrow transplants, these donor T lymphocytes may recognize the
recipient’s tissues as foreign and attack them. Physicians can reduce or
prevent this potentially fatal graft-versus-host (GVH) reaction by removing all
mature T lymphocytes from the organ or tissue before performing the
transplant.

Immune
C Deficiency

Deficiencies in immune function may be either inherited or acquired.

Inherited immune deficiencies usually reflect the failure of a gene important
to the generation or function of immune system components.

Some inherited diseases damage a person’s innate immunity by making

macrophages incapable of ingesting or breaking down invading organisms.
Individuals affected by these diseases are especially susceptible to
opportunistic infections—that is, infections by normally harmless organisms
that can flourish in a person whose immune system has been weakened.

DiGeorge syndrome is an inherited immune disorder in which a person has

no thymus and, therefore, cannot produce mature T lymphocytes. People
with this disorder can mount only limited humoral immune responses, and
their cell-mediated immune responses are severely limited.

The most extreme example of a hereditary immune deficiency is severe

combined immunodeficiency (SCID). Individuals with this disease completely
lack both T and B lymphocytes and thus have no adaptive immune
responses. People with SCID must live in a completely sterile environment, or
else they will quickly die from infections.

Acquired immune deficiencies can be caused by infections and also other

agents. For example, radiation therapy (see Radiology) and some kinds of
drugs used in treating disease reduce lymphocyte production, resulting in
damaged immune function. People undergoing such therapies must be
carefully monitored for lowered immune function and susceptibility to
infections. Environmental and lifestyle factors, such as poor nutrition or
stress, can also affect the immune system’s general status.
An infectious agent resulting in fatal immune deficiency is the human
immunodeficiency virus (HIV). This virus causes acquired immunodeficiency
syndrome (AIDS) by infecting and eventually destroying helper T cells.
Because helper T cells regulate all immune responses, their loss results in an
inability to make adaptive immune responses. This complete lack of immune
function makes individuals with AIDS highly susceptible to all infectious
agents.

Autoimmune
D Diseases

Autoimmunity is the immune response of the body turned against its own
cells and tissues. Autoimmune diseases may involve either cell-mediated
responses, humoral responses, or both. For example, in Type 1 diabetes, the
body makes an immune response against its insulin-producing cells and
destroys them, with the result that the body cannot use sugars. In
myasthenia gravis, the immune system makes antibodies against the normal
molecules that control neuromuscular activity, causing weakness and
paralysis. In rheumatic fever, the immune system makes antibodies that bind
to the heart’s valves, leading to permanent heart damage. In systemic lupus
erythematosus, commonly known as lupus, the body makes antibodies
against many different body tissues, resulting in widespread symptoms.

The mechanisms of autoimmune diseases are poorly understood, and thus

the basis for autoimmunity is unclear. Much research focuses on trying to
understand these mechanisms and should eventually result in cures.

Contributed By:
Michael P. Cancro
Microsoft ® Encarta ® 2009. © 1993-2008 Microsoft Corporation. All
rights reserved.